Department of Internal Medicine, Medical Oncology, Northwest Clinics Alkmaar, Wilhelminalaan 12, 1815, JD, Alkmaar, The Netherlands.
Invest New Drugs. 2018 Jun;36(3):513-516. doi: 10.1007/s10637-018-0576-y. Epub 2018 Feb 20.
Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib. Discussion The pharmacokinetics and pharmacodynamics of pazopanib are complex and characterized by a non-linear and time-dependent bioavailability. Pazopanib is almost completely bound to serum albumin (>99.9%). In this presented case, a low serum albumin (26 g/L) might have led to a higher free fraction of pazopanib, which could have resulted in more toxicity. Also, pazopanib is metabolised by the CYP3A4 isoform of the cytochrome P450 group. Low quantities of this enzyme may lead to an impaired and prolonged breakdown of the drug. Conclusion As far as we know this is the first report on pazopanib induced TLS. We advise further research in order to identify the exact mechanism behind TKI-induced TLS and the patients at risk of developing TLS.
简介 肿瘤溶解综合征（TLS）是一种由抗肿瘤治疗导致的快速细胞死亡引起的危及生命的紧急情况。在靶向治疗时代，它在肝癌（HCC）和肾细胞癌（RCC）等实体恶性肿瘤中越来越常见。 病例 我们描述了一例 58 岁男性的病例，该患者有 Memorial Sloan Kettering 癌症中心（MSKCC）预后不良转移性透明细胞肾细胞癌（mRCC）的病史，在开始使用酪氨酸激酶抑制剂（TKI）帕唑帕尼治疗后 6 天内发生了 TLS。 讨论 帕唑帕尼的药代动力学和药效学复杂，具有非线性和时间依赖性的生物利用度。帕唑帕尼几乎完全与血清白蛋白结合（>99.9%）。在本病例中，低血清白蛋白（26g/L）可能导致帕唑帕尼的游离分数更高，从而导致更多的毒性。此外，帕唑帕尼由细胞色素 P450 组的 CYP3A4 同工酶代谢。这种酶的数量减少可能导致药物的分解受损和延长。 结论 据我们所知，这是首例关于帕唑帕尼诱导 TLS 的报告。我们建议进一步研究，以确定 TKI 诱导 TLS 的确切机制以及易发生 TLS 的患者。
